Background Exhausting exercise reduces the mitochondrial DNA (mtDNA) content in the skeletal muscle of healthy subjects due to oxidative damage. Since patients with chronic obstructive pulmonary disease (COPD) suffer enhanced oxidative stress during exercise, it was hypothesised that the mtDNA content will be further reduced. Objective To investigate the effects of exercise above and below the lactate threshold (LT) on the mtDNA content of skeletal muscle of patients with COPD. Methods Eleven patients with COPD (6768 years; forced expiratory volume in 1 s (FEV 1 ) 4568%ref) and 10 healthy controls (6664 years; FEV 1 9067% ref) cycled 45 min above LT (65% peak oxygen uptake (V 9 O 2 peak) and another 7 patients (6566 years; FEV 1 5064%ref) and 7 controls (5669 years; FEV 1 9266%ref) cycled 45 min below their LT (50% V 9 O 2 peak). Biopsies from the vastus lateralis muscle were obtained before exercise, immediately after and 1 h, 1 day and 1 week later to determine by PCR the mtDNA/nuclear DNA (nDNA) ratio (a marker of mtDNA content) and the expression of the peroxisome proliferator-activated receptor-gcoactivator-1a (PGC-1a) mRNA and the amount of reactive oxygen species produced during exercise was estimated from total V 9 O 2 . Results Skeletal muscle mtDNA/nDNA fell significantly after exercise above the LT both in controls and in patients with COPD, but the changes were greater in those with COPD. These changes correlated with production of reactive oxygen species, increases in manganese superoxide dismutase and PGC-1a mRNA and returned to baseline values 1 week later. This pattern of response was also observed, albeit minimised, in patients exercising below the LT. Conclusions In patients with COPD, exercise enhances the decrease in mtDNA content of skeletal muscle and the expression of PGC-1a mRNA seen in healthy subjects, probably due to oxidative stress.

To cite this version:J. Zabaleta, B. Aguinagalde, M.G. Fuentes, N. Bazterargui, J.M. Izquierdo, et al.. Survival after lung metastasectomy for colorectal cancer: Importance of previous liver metastasis as a prognostic factor. EJSO -European Journal of Surgical Oncology, WB Saunders, 2011, 37 (9) This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. were performed on 84 patients. The median age of patients was 65.4 years, and 60% of patients were male. The 30-day mortality rate was 2%, and incidence of complications was 7%. The overall survival was 72 months, with 3-and 5-year survival rates of 70% and 54%, respectively. A total of 17 patients (20%) had previously undergone resection of liver metastasis. No significant differences were found in the distribution of what were supposed to be the main variables between patients with and without previous hepatic metastases. Multivariate analysis identified the following statistically significant factors affecting survival: previous liver metastasectomy (p=0.03), tumour-infiltrated pulmonary lymph nodes (p=0.04), disease-free interval ≥ 48 months (p=0.03), and presence of more than one lung metastasis (p<0.01). In patients with previous liver metastasis, the shorter the time between primary colorectal surgery and the hepatectomy, the lower the survival rate after pulmonary metastasectomy (p=0.048). M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT Conclusions:A previous history of liver metastasis shortens survival after lung metastasectomy. The time between hepatic resection and lung metastasectomy does not affect survival; however, patients with synchronous liver metastasis and colorectal neoplasia have poorer survival rates than those with metachronous disease.

Objective To compare the clinical characteristics and outcomes of patients with acute heart failure (AHF) according to clinical profiles based on congestion and perfusion determined in the emergency department (ED). Methods and results Overall, 11 261 unselected AHF patients from 41 Spanish EDs were classified according to perfusion (normoperfusion = warm; hypoperfusion = cold) and congestion (not = dry; yes = wet). Baseline and decompensation characteristics were recorded as were the main wards to which patients were admitted. The primary outcome was 1‐year all‐cause mortality; secondary outcomes were need for hospitalisation during the index AHF event, in‐hospital all‐cause mortality, prolonged hospitalisation, 7‐day post‐discharge ED revisit for AHF and 30‐day post‐discharge rehospitalisation for AHF. A total of 8558 patients (76.0%) were warm + wet, 1929 (17.1%) cold + wet, 675 (6.0%) warm + dry, and 99 (0.9%) cold + dry; hypoperfused (cold) patients were more frequently admitted to intensive care units and geriatrics departments, and warm + wet patients were discharged home without admission. The four phenotypes differed in most of the baseline and decompensation characteristics. The 1‐year mortality was 30.8%, and compared to warm + dry, the adjusted hazard ratios were significantly increased for cold + wet (1.660; 95% confidence interval 1.400–1.968) and cold + dry (1.672; 95% confidence interval 1.189–2.351). Hypoperfused (cold) phenotypes also showed higher rates of index episode hospitalisation and in‐hospital mortality, while congestive (wet) phenotypes had a higher risk of prolonged hospitalisation but decreased risk of rehospitalisation. No differences were observed among phenotypes in ED revisit risk. Conclusions Bedside clinical evaluation of congestion and perfusion of AHF patients upon ED arrival and classification according to phenotypic profiles proposed by the latest European Society of Cardiology guidelines provide useful complementary information and help to rapidly predict patient outcomes shortly after ED patient arrival.

The EAHFE Registry is the first European ED-based registry describing the characteristics, clinical course, and outcomes of a cohort resembling the universe of patients with AHF. Significant changes were observed over time in some aspects of AHF characteristics and management, but not in outcomes.